Panax quinquefolius saponins and panax notoginseng saponins attenuate myocardial hypoxia-reoxygenation injury by reducing excessive mitophagy.

OBJECTIVE: Panax quinquefolius saponins (PQS) and Panax notoginseng saponins (PNS) are key bioactive compounds in Panax quinquefolius L. and Panax notoginseng, commonly used in the treatment of clinical ischemic heart disease. However, their potential in mitigating myocardial ischemia-reperfusion injury remains uncertain. This study aims to evaluate the protective effects of combined PQS and PNS administration in myocardial hypoxia/reoxygenation (H/R) injury and explore the underlying mechanisms. METHODS: To investigate the involvement of HIF-1α/BNIP3 mitophagy pathway in the myocardial protection conferred by PNS and PQS, we employed small interfering BNIP3 (siBNIP3) to silence key proteins of the pathway. H9C2 cells were categorized into four groups: control, H/R, H/R + PQS + PNS, and H/R + PQS + PNS+siBNIP3. Cell viability was assessed by Cell Counting Kit-8, apoptosis rates determined via flow cytometry, mitochondrial membrane potential assessed with the JC-1 fluorescent probes, intracellular reactive oxygen species detected with 2',7'-dichlorodihydrofluorescein diacetate, mitochondrial superoxide production quantified with MitoSOX Red, and autophagic flux monitored with mRFP-GFP-LC3 adenoviral vectors. Autophagosomes and their ultrastructure were visualized through transmission electron microscopy. Moreover, mRNA and protein levels were analyzed via real-time PCR and Western blotting. RESULTS: PQS + PNS administration significantly increased cell viability, reduced apoptosis, lowered reactive oxygen species levels and mitochondrial superoxide production, mitigated mitochondrial dysfunction, and induced autophagic flux. Notably, siBNIP3 intervention did not counteract the cardioprotective effect of PQS + PNS. The PQS + PNS group showed downregulated mRNA expression of HIF-1α and BNIP3, along with reduced HIF-1α protein expression compared to the H/R group. CONCLUSIONS: PQS + PNS protects against myocardial H/R injury, potentially by downregulating mitophagy through the HIF-1α/BNIP3 pathway.

Chinese Proprietary Medicine Xianling Gubao Capsule for Osteoporosis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Objective: To assess the benefit and harm of Chinese medicine Xianling Gubao (XLGB) capsule compared to conventional medication or placebo to inform clinical practice. Methods: We included randomized controlled trials (RCTs) with Jadad score ≥3 of XLGB capsule compared to pharmaceutical medication, placebo, or no treatment for primary osteoporosis. We conducted searches in EMBASE, Cochrane CENTRAL, MEDLINE, China National Knowledge Infrastructure, VIP, Wanfang, and Chinese Biomedical Literature Database (Sino-Med) from their inception till November 13th, 2021. Study selection and data extraction were done by two authors independently. The methodological quality of the RCTs was assessed using Cochrane's risk of bias tool. The effect size was presented as risk ratio (RR) or mean difference (MD) with their 95% confidence interval (CI). Results: Our searches identified 2292 records and after exclusions, eight trials involving 846 participants were included. There was no statistically significant difference between conventional medications with or without XLGB on new fracture (RR: 0.50, 95% CI: [0.13, 1.87]). Quality of life by SF-36 questionnaire of XLGB plus calcium carbonate, vitamin D3, and calcitriol was improved than that of without XLGB (MD: 6.72 scores, 95% CI: [2.82, 10.62]). XLGB increased bone mineral density similarly as calcium carbonate plus vitamin D3 (MD: 0.21, 95% CI: [-0.16, 0.58]) or as alendronate sodium, calcium carbonate plus vitamin D3 (MD: 0.00, 95% CI: [-0.10, 0.10]), but it had no additional effect as an add-on treatment to conventional medications (MD: 0.13, 95% CI: [-0.12, 0.37]). XLGB relieved pain via visual analog scale more effectively when combined with medications (MD: -1.55 score, 95% CI: [-2.47, -0.63]). XLGB as monotherapy did not increase adverse events (RR: 0.63, 95% CI: [0.28, 1.41]), or as an add-on treatment (RR: 0.25, 95% CI: [0.03, 2.16]). Conclusion: This systematic review shows that XLGB capsule appears to be safe and has a beneficial effect on the quality of life and pain relief when used alone or in combination with conventional medications in osteoporosis patients. Further large, rigorous trials are warranted to test its long-term benefit.

Cardiovascular safety of celecoxib in rheumatoid arthritis and osteoarthritis patients: A systematic review and meta-analysis.

OBJECTIVE: To assess the cardiovascular safety of celecoxib compared to non-selective non-steroid anti-inflammatory drugs or placebo. METHODS: We included randomized controlled trials of oral celecoxib compared with a non-selective NSAID or placebo in rheumatoid arthritis and osteoarthritis patients. We conducted searches in EMBASE, Cochrane CENTRAL, MEDLINE, China National Knowledge Infrastructure, VIP, Wanfang, and Chinese Biomedical Literature Database. Study selection and data extraction were done by two authors independently. The risk of bias was assessed using Cochrane's risk-of-bias Tool for Randomized Trials. The effect size was presented as a risk ratio with their 95% confidence interval. RESULTS: Until July 22nd, 2021, our search identified 6279 records from which, after exclusions, 21 trials were included in the meta-analysis. The overall pooled risk ratio for Antiplatelet Trialists Collaboration cardiovascular events for celecoxib compared with any non-selective non-steroid anti-inflammatory drugs was 0.89 (95% confidence interval: 0.80-1.00). The pooled risk ratio for all-cause mortality for celecoxib compared with non-selective non-steroid anti-inflammatory drugs was 0.81 (95% confidence interval: 0.66-0.98). The cardiovascular mortality rate of celecoxib was lower than non-selective non-steroid anti-inflammatory drugs (risk ratio: 0.75, 95% confidence interval: 0.57-0.99). There was no significant difference between celecoxib and non-selective non-steroid anti-inflammatory drugs or placebo in the risk of other cardiovascular events. CONCLUSION: Celecoxib is relatively safe in rheumatoid arthritis and osteoarthritis patients, independent of dose or duration. But it remains uncertain whether this would remain the same in patients treated with aspirin and patients with established cardiovascular diseases.

Physical Therapies for Psychosomatic Symptoms and Quality of Life Induced by Aromatase Inhibitors in Breast Cancer Patients: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the effects of Physical Therapies (PTs) on improvement in psychosomatic symptoms and quality of life (QOL) in breast cancer patients. DATA SOURCES: Seven databases (MEDLINE, EMBASE, Cochrane CENTRAL, China National Knowledge Infrastructure, Wangfang, VIP, and China Biology Medicine disc databases) were systematically searched from the database inception through May 18, 2021. STUDY SELECTION: Randomized controlled trials (RCTs) which compared acupuncture or exercise with a sham control or usual care for the treatment of aromatase inhibitors (AIs)-related psychosomatic symptoms and QOL. DATA EXTRACTION AND SYNTHESIS: Data were screened and extracted independently using predesigned forms. The quality of RCTs was assessed with the Cochrane Handbook for Systematic Reviews of Interventions. The effect size was calculated via random-effects modeling. The quality of evidence was evaluated with the Grading of Recommendations Assessment, Development and Evaluation approach. MAIN OUTCOMES AND MEASURES: The score of pain was measured with BPI scale and Western Ontario and the McMaster Universities Index (WOMAC) scale. Emotional state was measured with Pittsburgh Sleep Quality Index (PSQI), Hospital Anxiety and Depression Scale (HADS-A), and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue). The QOL score was measured by self-reported measurements, including the Functional Assessment of Cancer Therapy-General (FACT-G) scale and 36-Item Short Form Survey (SF-36) scale. RESULTS: Eleven RCTs (with 830 patients) were included in the systematic review, and data from 10 RCTs (with 798 patients) were used in the meta-analysis. Results showed acupuncture significantly reduced worst pain scores (P < 0.00001, I 2 = 83.5%) [SMD = -0.81, 95% CI (-1.51, -0.11)], but the effect of exercise therapies was not significant in overall change in worst pain scores (P =0.006, I 2 = 72.3%) [SMD = -0.30, 95% CI (-0.76, 0.16)]. Both acupuncture and exercise resulted in little to no difference in overall change in HADS-A subscale (P = 0.026<0.05, I 2 = 79.8%) [WMD = -0.21, 95% CI (-3.44, 3.03)], PSQI subscale (P = 0.488, I 2 = 0%) [WMD = 0.98, 95% CI (-0.57, 2.53)], and FACIT-Fatigue subscale (P = 0.022<0.05, I 2 = 81.0%) [WMD = 1.6, 95% CI (-5.75, 8.94)]. Exercise (compared with usual care) was associated with improving overall change in health-related QOL (subscales of SF-36 tool) (P = 0, I 2 = 72.1%) [WMD = 7.97, 95% CI (5.68, 10.25)] and cancer-specific QOL (subscales of FACT-G tool) (P = 0.304, I 2 = 16%) [WMD = 1.16, 95% CI (0.34, 1.97)]. CONCLUSIONS AND RELEVANCE: This systematic review and meta-analysis suggested that based on moderate-level evidence, acupuncture was associated with significant reductions in pain intensity, and exercise might improve QOL in breast cancer patients treated with AIs. However, in psychosomatic symptoms such as anxiety, sleep disturbance, and fatigue, acupuncture and exercise training did not result in significant improvements.

Promising Therapeutic Candidate for Myocardial Ischemia/Reperfusion Injury: What Are the Possible Mechanisms and Roles of Phytochemicals?

Percutaneous coronary intervention (PCI) is one of the most effective reperfusion strategies for acute myocardial infarction (AMI) despite myocardial ischemia/reperfusion (I/R) injury, causing one of the causes of most cardiomyocyte injuries and deaths. The pathological processes of myocardial I/R injury include apoptosis, autophagy, and irreversible cell death caused by calcium overload, oxidative stress, and inflammation. Eventually, myocardial I/R injury causes a spike of further cardiomyocyte injury that contributes to final infarct size (IS) and bound with hospitalization of heart failure as well as all-cause mortality within the following 12 months. Therefore, the addition of adjuvant intervention to improve myocardial salvage and cardiac function calls for further investigation. Phytochemicals are non-nutritive bioactive secondary compounds abundantly found in Chinese herbal medicine. Great effort has been put into phytochemicals because they are often in line with the expectations to improve myocardial I/R injury without compromising the clinical efficacy or to even produce synergy. We summarized the previous efforts, briefly outlined the mechanism of myocardial I/R injury, and focused on exploring the cardioprotective effects and potential mechanisms of all phytochemical types that have been investigated under myocardial I/R injury. Phytochemicals deserve to be utilized as promising therapeutic candidates for further development and research on combating myocardial I/R injury. Nevertheless, more studies are needed to provide a better understanding of the mechanism of myocardial I/R injury treatment using phytochemicals and possible side effects associated with this approach.